特定于乌比奎丁的蛋白酶21对癌细胞线粒体功能至关重要,并调节细胞的增殖和迁移
Magdalena Kulma1, Bartłomiej Hofman1, Małgorzata Szostakowska-Rodzoś1
1Molecure SA, Warsaw, Poland.
The Journal of biological chemistry
|September 21, 2024
概括
删除USP21,一个二基因酶,通过减少STAT3激活和线粒体功能,损害癌细胞代谢. 这为癌症治疗提供了针对USP21的新治疗策略.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 乌比基特异性蛋白酶 (USP) 是调节蛋白质稳定性和功能的二维基基酶.
- USP21在维持细胞平衡中发挥作用,并因其调节致癌蛋白质稳定性而与致癌症产生有关.
- 了解USP21在癌细胞代谢中的作用对于开发向疗法至关重要.
研究的目的:
- 为了研究USP21删除对癌细胞代谢的影响.
- 探索USP21,STAT3激活和癌细胞中的线粒体功能之间的关系.
- 确定针对USP21.21的潜在治疗策略.
主要方法:
- 对USP21淘汰赛 (KO) HAP-1细胞进行转录和蛋白质组分析.
- 评估STAT3激活和下游基因/蛋白质表达.
- 测量线粒体呼吸和ATP的产生.
主要成果:
- 删除USP21严重影响涉及线粒体功能的基因和蛋白质.
- 缺乏USP21会减少STAT3的激活及其依赖的信号通路.
- 在USP21KO细胞中观察到线粒体呼吸和ATP产生受损,导致抑制增殖和迁移.
结论:
- 内生USP21对于维持线粒体功能和癌细胞中的STAT3活性至关重要.
- 向USP21破坏癌细胞能量代谢,为抗癌疗法提供了一个有希望的途径.
- 抑制USP21为控制瘤细胞能量状态提供了新的机制.
相关概念视频
The Proteasome
818
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
818
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
Anaphase Promoting Complex
2.8K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.8K
Translocation of Proteins into the Mitochondria
3.1K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.1K
Regulated Protein Degradation
7.2K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
7.2K


